Clonal origin and genomic diversity in Lynch syndrome-associated endometrial cancer with multiple synchronous tumors: Identification of the pathogenicity of MLH1 p.L582H.

Lynch syndrome-associated endometrial cancer patients often present multiple synchronous tumors and this assessment can affect treatment strategies. We present a case of a 27-year-old woman with tumors in the uterine corpus, cervix, and ovaries who was diagnosed with endometrial cancer and exhibited cervical invasion and ovarian metastasis. Her family history suggested Lynch syndrome, and genetic testing identified a variant of uncertain significance, MLH1 p.L582H. We conducted immunohistochemical staining, microsatellite instability analysis, and Sanger sequencing for Lynch syndrome-associated cancers in three generations of the family and identified consistent MLH1 loss. Whole-exome sequencing for the corpus, cervical, and ovarian tumors of the proband identified a copy-neutral loss of heterozygosity (LOH) occurring at the MLH1 position in all tumors. This indicated that the germline variant and the copy-neutral LOH led to biallelic loss of MLH1 and was the cause of cancer initiation. All tumors shared a portion of somatic mutations with high mutant allele frequencies, suggesting a common clonal origin. There were no mutations shared only between the cervix and ovary samples. The profiles of mutant allele frequencies shared between the corpus and cervix or ovary indicated that two different subclones originating from the corpus independently metastasized to the cervix or ovary. Additionally, all tumors presented unique mutations in endometrial cancer-associated genes such as ARID1A and PIK3CA. In conclusion, we demonstrated clonal origin and genomic diversity in a Lynch syndrome-associated endometrial cancer, suggesting the importance of evaluating multiple sites in Lynch syndrome patients with synchronous tumors.

Relationship between masseter muscle activity during wakefulness and temporomandibular disorder-related symptoms.

BACKGROUND: Masseter muscle activity during wakefulness may be associated with temporomandibular disorder (TMD)-related symptoms, psychosocial status and pain-related disability; however, this relationship is unclear. OBJECTIVES: This study aimed to determine the relationship between masseter muscle electromyography (EMG) burst/duration during wakefulness and TMD-related symptoms, psychosocial status and pain-related disability. METHODS: Sixty participants were assessed masseter muscle activity during wakefulness using a data-logger-type ultraminiature EMG system and TMD-related symptoms, psychosocial status and pain-related disability through Axis I and II of the diagnostic criteria for TMD (DC/TMD). EMG bursts lasting longer than 0.25 s but less than 2.0 s and those lasting longer than 2.0 s were classified as phasic and tonic bursts, respectively. RESULTS: Participants with palpation-related pain in the temporalis and masseter muscles, as assessed through the DC/TMD examination form in Axis I, had more bursts (number/h) (p = .035 and p = .009, respectively) and longer duration (time/h) (p = .013 and p = .004, respectively) of tonic bursts of the masseter muscle during wakefulness. Participants with palpation-related pain in the masseter muscles had higher oral behaviour scores during wakefulness using Axis II (p = .001), which affected the number and duration of tonic bursts of the masseter muscle activity during wakefulness (p = .011 and p = .007, respectively). CONCLUSION: As tonic bursts mainly reflect clenching, individuals with pain in the masseter muscles by palpation may have a high frequency and longer duration of clenching, as well as a high frequency of oral behaviours during wakefulness.

Endometrial Cancer with and without Endometriosis: Clinicopathological Differences.

Endometriosis is known to be associated with an increased risk of endometrioid and clear cell ovarian cancer. However, the association between endometriosis and endometrial cancer is controversial. Therefore, we retrospectively analyzed the medical records of women with endometrial cancer who had undergone surgery at our institution to evaluate the clinicopathological relationship between endometrial cancer and endometriosis. The study included 720 women pathologically diagnosed with endometrial cancer at our hospital between 2000 and 2020. The participants were allocated to two groups of patients with endometrial cancer: patients with endometriosis (n = 101) and patients without endometriosis (n = 619). Endometrial cancer patients with endometriosis were significantly younger (median age 54.0 vs. 58.0; p = 0.002). In addition, endometrial cancer patients with endometriosis had fewer pregnancies and deliveries (median pregnancy 1.58 vs. 1.99; p = 0.019, median delivery 1.25 vs. 1.56; p = 0.012). The percentage of patients classified as stage IA was significantly higher in those with endometrial cancer with endometriosis (68.3% vs. 56.4%; p = 0.029). In the analysis of synchronous ovarian cancer, the percentage of dual primary cancer was higher in patients with endometriosis (14.9% vs. 1.6%; p < 0.001). The association of young-onset early-stage endometrial cancer with endometriosis is an important finding that cannot be ignored clinically.

A snare maneuver to reposition self-expandable aortic valve after transcatheter replacement of surgically implanted valve.

In this case, we successfully repositioned the transcatheter heart valve (THV) by pulling it with a snare inserted via the right brachial artery. Attempting to pull the THV via the femoral approach was not successful, due to the vector of the pulling force not being coaxial. Changing the direction of the force by switching to an approach from the right brachial artery successfully prevented perivalvular leakage. While there are previous case reports of repositioning an implanted transcatheter valve in a native valve using a gooseneck snare, to our knowledge, this is the first case of successfully repositioning an implanted transcatheter valve in a valve-in-valve procedure using the precise assessment that can be achieved with intra-procedural transesophageal echocardiography. Learning objective: Perivalvular leakage (PVL) is a major problem after transcatheter aortic valve replacement. In this case, we experienced PVL after implantation of self-expandable transcatheter heart valve (THV) inside the previously inserted Mosaic bioprosthetic valve. Depth of the implanted valve was too low into left ventricle accessed with transesophageal echocardiogram. It is barely known whether THV in surgical implanted aortic valve could be repositioned using snare maneuver, but we successfully pulled the valve via brachial artery and PVL was controlled.

A retrospective study of Pipelle endometrial biopsy for ovarian, fallopian tube, and peritoneal cancers.

OBJECTIVES: Although the Pipelle endometrial biopsy is widely performed as a practical and minimally invasive test for endometrial disease(s), its effectiveness in ovarian cancer has not been explored. The aim of the present study was to evaluate the results of Pipelle endometrial biopsy for ovarian, fallopian tube, and peritoneal cancers. METHODS: A pre-treatment Pipelle-endometrial biopsy was performed in 90 patients with ovarian, fallopian tube, or peritoneal cancers between January 2014 and November 2021. We retrospectively analysed the association between the results of Pipelle endometrial biopsy and clinicopathological data. Moreover, we evaluated their impact on the following treatment in advanced cases initially treated with chemotherapy. RESULTS: The sensitivity and false-negative rates for Pipelle endometrial biopsy were 25/90 (27.8%) and 65/90 (72.2%) in all patients, respectively, and 23/56 (41.0%) and 33/56 (58.9%) in cases with advanced disease (stages III and IV), respectively. Pipelle-positive endometrial biopsy-positive (Pipelle-positive) was not observed in 29 patients with clinical stage I disease, and Pipelle-positive patients exhibited significantly more high-grade serous carcinomas, and positive peritoneal, endometrial, and cervical cytologies than Pipelle-endometrial biopsy-negative cases. Surgical pathology was confirmed in 23 Pipelle-positive patients, and 17/23 (74.0%) had the same diagnosis as that for Pipelle endometrial biopsy. Conversely, 6/23 (26.0%) patients exhibited a minor diagnostic discrepancy between Pipelle endometrial biopsy and surgical pathology. Nineteen of the 38 (50.0%) patients initially treated with chemotherapy were identified as Pipelle-positive, contributing to a prompt histological diagnosis and pre-treatment tumour sampling. Companion diagnostic tests were performed using Pipelle endometrial biopsy samples from 4 inoperable patients. CONCLUSION: Although the positive rate of Pipelle endometrial biopsy in ovarian, fallopian tube, and peritoneal cancers is low, Pipelle endometrial biopsy may enable prompt histological diagnosis and initiation of chemotherapy while collecting tumour tissue for genetic testing in some cases with advanced disease.

The effectiveness of pre-treatment Pipelle endometrial biopsy for ovarian, fallopian tube, and peritoneal cancers remains unclear. This study demonstrated that Pipelle endometrial biopsy may enable prompt histological diagnosis and initiation of chemotherapy while collecting tumour tissue for genetic testing in some cases with advanced disease. This was a single-centre, retrospective study; as such, the effectiveness of Pipelle endometrial biopsy should be evaluated in larger prospective studies, including comparisons with other tumour sampling methods.

Age and long-term outcomes of patients with venous thromboembolism: From the COMMAND VTE Registry.

BACKGROUND: There is still a scarcity of data on the relation between age and long-term clinical outcomes of patients with venous thromboembolism (VTE). METHODS: The COMMAND VTE Registry was a multicenter registry enrolling 3027 consecutive patients with acute symptomatic VTE in Japan between January 2010 and August 2014. We divided the entire cohort into 3 groups: patients aged <65 years (N = 1100, 36.7%), patients aged 65 ≤ and ≤ 80 years (N = 1314, 43.4%), and patients aged >80 years (N = 603, 19.9%). RESULTS: Discontinuation of anticoagulation therapy during the follow-up period was most frequent in patients aged <65 years (44%, 38% and 33%, P < 0.001). The cumulative 5-year incidences were 12.7%, 9.8% and 7.4% for recurrent VTE, 10.8%, 12.2% and 14.9% for major bleeding, and 23.0%, 31.4%, and 38.6% for all-cause death. Adjusting for cofounders and taking into account the competing risk of all-cause death, the lower risk of patients aged >80 years, and those aged 65 ≤ and ≤ 80 years relative to those aged <65 years remained significant for recurrent VTE (65 ≤ age ≤ 80 years, HR: 0.71, 95%CI: 0.53-0.94, P = 0.02; age > 80 years, HR: 0.59, 95%CI: 0.39-0.89, P = 0.01), and the risk remained insignificant for major bleeding (65 ≤ age ≤ 80 years, HR: 1.00, 95%CI: 0.76-1.31, P = 0.98; age > 80 years, HR: 1.17, 95%CI: 0.83-1.65, P = 0.37). CONCLUSIONS: In the current real-world VTE registry, there was no significant difference in the risk of major bleeding depending on different age groups, while younger patients showed an excess risk for recurrent VTE compared with older patients.

Predictors of success and puncture site complications in the distal radial approach.

The distal radial approach (DRA) has been proposed as an alternative approach for coronary angiography (CAG) and percutaneous coronary intervention (PCI); however, the predictors of DRA failure and puncture site complications are unclear. Among 7153 consecutive patients undergoing CAG or PCI between November 2018 and January 2021, 3610 patients undergoing CAG or PCI with DRA were analyzed. The primary endpoint of this study was the procedural success, and the secondary endpoint of this study was puncture site complications during procedure. Puncture site complications during procedure were defined as a composite of major bleeding, minor bleeding, arteriovenous fistula, pseudoaneurysm, and neuropathy. The DRA success rate and the puncture site complication rate were 90.4% and 7.7%, respectively. The predictors of DRA failure were low body weight and dual antiplatelet therapy; those of DRA success were PCI and ultrasonography-guided DRA; those of puncture site complications during procedure were low body weight, peripheral arterial disease, dual antiplatelet therapy, anticoagulant therapy, and PCI; and that of no puncture site complications were previous PCI and ultrasonography-guided DRA. The negative predictors of DRA success with no puncture site complication during procedure were low body weight and dual antiplatelet therapy. The positive predictor of DRA success with no puncture site complication during procedure was ultrasonography-guided DRA. We identified the predictors of DRA failure and puncture site complications during procedure in patients undergoing CAG and PCI with DRA. Ultrasonography-guided DRA was associated with a high DRA success rate and a low puncture site complication rate in patients undergoing CAG or PCI with DRA.

Comparison and Validation of Long-Term Bleeding Events for Academic Bleeding Risk (ARC-HBR) Criteria and Contemporary Risk Scores for Percutaneous Coronary Intervention With a Second-Generation Drug Eluting Stent.

BACKGROUND: The Academic Research Consortium for High Bleeding Risk (ARC-HBR) defined a consensus clinical criterion for patients at HBR undergoing percutaneous coronary intervention (PCI). This study aimed to validate and compare the ARC-HBR criteria and the contemporary risk score for long-term bleeding outcomes using a cohort of patients undergoing PCI.Methods and Results: This study analyzed 3,410 patients who underwent PCI between 2010 and 2013. The endpoint was defined as incidence of The Bleeding Academic Research Consortium 3 or 5 bleeding events. In addition to ARC-HBR, this study validated the predictability of the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score, Patterns of non-adherence to Anti-platelet Regimens In Stented patients (PARIS) bleeding score, and Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) bleeding scores for bleeding events. There was a trend toward an increase in bleeding events, as the risk score increased for all bleeding risk scores used in this study. The ARC-HBR criteria had higher diagnostic sensitivity for bleeding events than other bleeding risk scores. CONCLUSIONS: Patients with a higher number of risk factors in each of the four bleeding risk scores had a higher risk of long-term bleeding events. In comparison to other contemporary risk scores, the ARC-HBR criteria were more sensitive in the identification of patients with bleeding events in the long-term.

Comparison of original and modified Academic Research Consortium for High Bleeding Risk definitions in real-world practice.

BACKGROUND: The Academic Research Consortium for High Bleeding Risk (ARC-HBR) defined high bleeding risk (HBR) in patients undergoing percutaneous coronary intervention. We have reported a simplified HBR (S-HBR), excluding six items with prevalences under 1% from ARC-HBR. The Japanese Circulation Society developed an HBR specific to Japanese (J-HBR), adding three items to ARC-HBR in consideration of ethnicity. Data comparing each HBR are scarce. METHODS: Patients treated with second-generation drug-eluting stents between January 2010 and December 2013 were enrolled, in whom all items of ARC-HBR, and the incidences of major bleeding and ischemic events were examined. Also, the diagnostic values of ARC-HBR, S-HBR, and J-HBR at 1 and 7 years post procedure were compared by using receiver-operating characteristic curves. RESULTS: The study sample consisted of 3430 patients. Mean follow-up period was 2299 ±â€¯904 days. The incidence of major bleeding at 1 and 7 years in each definition was as follows: ARC-HBC, 3.3% and 10.6%; S-HBR, 3.3% and 10.7%; and J-HBR, 2.9% and 10.0%. The diagnostic value of J-HBR for major bleeding at 1 year was lower than that of ARC-HBR (C statistics 0.64 vs. 0.68, p < 0.001). Other diagnostic values of S-HBR and J-HBR were comparable to those of ARC-HBR. CONCLUSIONS: S-HBR was as useful as ARC-HBR in predicting both short- and long-term HBR, and J-HBR is useful for predicting long-term HBR.

Gastrointestinal and Intracranial Bleeding Events After Second-Generation Drug-Eluting Stent Implantation　- Their Association With High Bleeding Risk, Predictors, and Clinical Outcomes.

BACKGROUND: Gastrointestinal bleeding (GIB) and intracranial bleeding (ICB) are frequently observed as major bleeding events after percutaneous coronary intervention (PCI); however, there are few reports on these predictors and their association with the Academic Research Consortium for High Bleeding Risk (ARC-HBR).Methods and Results: The study included 3,453 patients who underwent PCI with second-generation drug-eluting stents between 2010 and 2013. Mean follow up was 2,663±596 days. The cumulative incidences of GIB and ICB were significantly higher in the HBR group than in the non-HBR group (6.3% vs. 1.9%, P<0.001, 5.5% vs. 2.3%, P<0.001). Older age, oral anticoagulant (OAC), and severe chronic kidney disease were independent predictors of GIB (hazard ratios [HR], 1.64; 95% confidence intervals [CI], 1.11-2.41; P=0.012; HR, 1.94; 95% CI, 1.23-3.05; P=0.004; HR, 1.80; 95% CI, 1.02-3.19, P=0.043 respectively), and low body weight, OAC, and left main coronary artery stenting were independent predictors of ICB by multivariate logistic regression analysis (HR, 1.83; 95% CI, 1.20-2.80; P=0.005; HR, 2.04; 95% CI, 1.31-3.19; P=0.002; HR, 1.79; 95% CI, 1.18-2.70; P=0.006 respectively). CONCLUSIONS: ARC-HBR was consistently associated with GIB and ICB within a 7-year period. GIB and ICB had three predictors each. Of these, only OAC administration was common, and the other two were different.

Incidence, Risk Factors, and Prognosis of Cholesterol Crystal Embolism Because of Percutaneous Coronary Intervention.

Cholesterol crystal embolism (CCE) is a rare but serious complication of percutaneous coronary intervention (PCI). However, its incidence, risk factors, and prognosis in the contemporary era are not well known. We included 23,184 patients who underwent PCI in our institution between January 2000 and December 2019 in this study. The diagnosis of CCE was made histologically or by the combination of cutaneous signs and specific blood test results. In patients with CCE, we evaluated the incidence, risk factors, and prognosis. A total of 88 patients (0.38%) were diagnosed with CCE. The incidence of CCE seemed to decline through the investigated 20 years. Positive predictors of CCE were age ≥70 years (68% vs 59%, p = 0.012), aortic aneurysm (23% vs 7.2% p <0.001), and a femoral approach (71% vs 45%, p <0.001), whereas a negative predictor of CCE was the use of an inner sheath (63% vs 77%, p <0.001). The rate of 1-year mortality and the requirement for chronic hemodialysis within 1 year after PCI in patients with CCE were 10% and 11%, respectively. The use of an inner sheath and a nonfemoral approach was associated with a lower incidence of CCE. In conclusion, because the prognosis of patients with CCE is still poor, preprocedural identification of high-risk patients and selection of low-risk procedures could be important for preventing CCE.

Percutaneous coronary intervention for left main coronary artery malperfusion in acute type A aortic dissection.

The clinical outcomes of patients undergoing percutaneous coronary intervention (PCI) for left main coronary artery (LMCA) malperfusion caused by acute type A aortic dissection (AAAD) remains largely unexplored. The aim of this study was to determine the clinical outcomes of patients undergoing PCI for LMCA malperfusion caused by AAAD. We examined nine consecutive patients undergoing PCI for LMCA malperfusion caused by AAAD between 1995 and 2020. The mean age was 55.4 ± 7.7 years. Eight patients presented cardiogenic shock, and five patients cardiopulmonary arrest. Two patients were diagnosed with AAAD before coronary angiography using computed tomography and transthoracic echocardiography, respectively, and in the other seven patients after coronary angiography using other modalities. Four patients underwent PCI on intra-aortic balloon pumping support, and four patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO) support, including one patient on both. PCI was successful in eight patients, with final thrombolysis in myocardial infarction grade 2 or 3. The four patients on VA-ECMO did not undergo aortic dissection repair due to poor recovery of cardiac function and died during the hospital stay, and the other five patients had successful PCI, underwent aortic dissection repair, and remained alive at 5 year follow-up. In conclusion, LMCA malperfusion caused by AAAD seemed to have clinical presentations and electrocardiogram changes similar to acute coronary syndrome. PCI and subsequent surgical aortic repair saved the lives of all AAAD patients with LMCA malperfusion who had not required VA-ECMO.

Delayed stenosis regression after drug-coated balloon angioplasty for femoropopliteal artery lesions.

Paclitaxel has the potential for inducing lumen enlargement by vessel enlargement, healing of dissection, and plaque regression. This study was carried out to determine the possibility of and the relevant factors of delayed stenosis regression after drug-coated balloon (DCB) angioplasty for femoropopliteal (FP) artery lesions. A total 105 de novo FP lesions were finalized with DCB angioplasty in our institute between May 2018 and June 2020. Among them, cases in which residual stenosis was detected by duplex ultrasonography (DUS) after the procedure were included in this study. Significant stenosis was defined as peak systolic velocity ratio ≥ 2.4 by DUS. Follow-up DUS was routinely performed 6 months after the procedure, and we defined cases without stenosis as cases of delayed stenosis regression according to the follow-up DUS. DUS showed that 26 (25.5%) of 102 lesions had residual stenosis after DCB angioplasty, and delayed stenosis regression was observed in 12 (57.1%) of 21 lesions 6 months after the procedure. The percentage of lesions containing calcified plaque as detected by intravascular ultrasound analysis was significantly higher in the non-regression group than in the regression group (18.2% vs. 77.8%, p = 0.02). Vessel remodeling and dissection patterns were not associated with delayed stenosis regression. The results of our analyses indicate that delayed stenosis regression may occur after DCB angioplasty for FP lesions in more than half of cases with residual stenosis. Delayed stenosis regression may be difficult in cases of calcified lesions.

Incidence, predictors, and clinical outcomes of mechanical circulatory support-related complications in patients with cardiogenic shock.

BACKGROUND: Mechanical circulatory support (MCS) is essential to maintain the hemodynamics in selected patients with cardiogenic shock (CS). However, little is known about predictors and clinical impact of device-related complications on clinical outcomes in patients with MCS. METHODS: We retrospectively reviewed consecutive 477 patients who received veno-arterial extracorporeal membrane oxygenation (VA-ECMO), Impella (Abiomed, Danvers, MA, USA), and intra-aortic balloon pump (IABP) from January 2012 to May 2020. After excluding patients with only VA-ECMO and patients with MCS for procedural support, 403 patients were included in this study. Predictors and clinical outcomes of device-related complications were analyzed. Furthermore, complication rates were compared between Impella and IABP groups in patients with and without VA-ECMO. RESULTS: Hemolysis, major bleeding defined by Bleeding Academic Research Consortium type 3 or 5 bleeding, thromboembolic events, and ischemic stroke were observed in 42 (10.4%), 150 (37.2%), 52 (12.9%), and 30 patients (7.4%), respectively. Patients with major bleeding had a higher in-hospital mortality than those without major bleeding (31.2% vs. 56.0%, p<0.001), whereas hemolysis (47.6% vs. 52.4%, p=0.32), thromboembolic events (38.5% vs. 40.7%, p=0.76), and ischemic stroke (48.5% vs. 39.7%, p=0.33) did not increase the in-hospital mortality. In multivariate analysis, both Impella and VA-ECMO were independent predictors of major bleeding and thromboembolic events. However, in-hospital mortality was similar between the Impella and IABP groups irrespective of the VA-ECMO insertion. CONCLUSIONS: Among several important complications in CS patients with MCS, major bleeding events most strongly affected the mortality. Implanted MCS type was associated with the device-related complications.

Clinical results of image-guided interstitial brachytherapy with or without external beam radiotherapy for postsurgical vaginal recurrence of cervical and endometrial cancers.

PURPOSE: This study aimed to evaluate the clinical outcome and efficacy of image-guided interstitial brachytherapy (ISBT) for postsurgical vaginal recurrence of cervical and endometrial cancers. MATERIALS AND METHODS: The study included 11 patients who received CT-based image-guided high-dose-rate ISBT with or without external beam radiotherapy (EBRT). Local control, progression-free survival, and treatment-related toxicities were evaluated retrospectively. RESULTS: Of the 11 patients, 4 underwent ISBT with EBRT and the other 7 ISBT alone; two of the latter patients received previous pelvic radiotherapy. After a median follow-up of 43.9 months (range 3.9-92.7 months), the 2-year local control rate was 100%. The median equivalent doses in 2 Gy fractions received by at least 90% of the clinical target volume for ISBT with versus without EBRT were 82.2 Gy (range 60.4-84.2 Gy) versus 69.0 Gy (range 50.8-98.2 Gy). The 2-year progression-free survival rates after ISBT with versus without EBRT were 75% versus 80%, and the difference was not significant (p = 0.74). Grade 3 late toxicities occurred in two patients. CONCLUSION: Our radiotherapy strategy using image-guided ISBT, either with or without EBRT, for postsurgical vaginal recurrence showed effective treatment outcomes.

Renal cortex thickness and changes in renal function after transcatheter aortic valve implantation.

BACKGROUND: The association between renal morphological findings and changes in renal function in patients undergoing transcatheter aortic valve implantation (TAVI) is unexplored. AIMS: We aimed to investigate the association between renal morphological findings and changes in renal function in patients undergoing TAVI. METHODS: Among 283 consecutive patients undergoing TAVI between 2018 and 2021, the study sample included 224 patients. Renal morphological measurements were performed by preoperative multidetector computed tomography. Estimated glomerular filtration rate (eGFR) improvement and deterioration were defined as positive or negative changes in an eGFR of ≥10% one month after TAVI. The renal cortex thickness index was defined as the ratio of total renal cortex thickness to body surface area. RESULTS: The incidences of eGFR improvement and deterioration were 33.9% and 24.1%, respectively. The renal cortex thickness index had a significant correlation with changes in eGFR (r=0.34, p<0.01). The index of the area under the curve of renal cortex thickness for eGFR improvement and deterioration were 0.73 and 0.68, respectively. The cut-off values were 5.82 mm/m2 for eGFR improvement (odds ratio [OR]: 0.10; 95% confidence interval: 0.05-0.20; p<0.01) and 4.89 mm/m2 for eGFR deterioration (OR: 9.07; 95% confidence interval: 4.55-18.6; p<0.01). CONCLUSIONS: The renal cortex thickness index was associated with changes in renal function in patients who underwent TAVI. Its measurements might be useful for predicting the renal function change in patients undergoing TAVI.

Vulvar Extramammary Paget Disease Detected by Cytology for Cervical Cancer Screening: A Case Report and Literature Review.

BACKGROUND Vulvar extramammary Paget disease (EMPD) with abnormal cervical cytology is extremely rare. We encountered a case of secondary EMPD derived from urothelial carcinoma diagnosed after cytological examination for cervical cancer screening. We diagnosed the case promptly owing to suspicion based on the patient's medical history and vulvar appearance. We report the case and present a review of published cases of EMPD with abnormal cervical cytology. CASE REPORT A 77-year-old Japanese woman visited a hospital because cervical cancer screening raised the suspicion of adenocarcinoma. Findings of the cytological examinations of the cervix, endometrium, and urethral meatus corresponded to those of other malignant neoplasms of the Bethesda system. The patient had undergone total urethral cystectomy for urothelial carcinoma 5 years earlier. In our hospital, we found erythema extending from the urethral meatus to the vulva and performed a vulvar biopsy based on the suspicion of recurrence of the urothelial carcinoma. We diagnosed secondary EMPD derived from the urothelial carcinoma based on the findings of Paget cells in the epithelium and immunohistochemistry. CONCLUSIONS A review of all the reported cases of EMPD with abnormal cervical cytology shows that the frequency of primary lesions is high in primary EMPD and secondary EMPD derived from urothelial carcinoma. These cases demonstrated the difficulty of suspecting EMPD based on cervical cytology alone. It should be considered that the cells derived from vulvar EMPD can be observed in cervical cytology, particularly in patients with a history of primary EMPD or urothelial carcinoma and with vulvar symptoms.

Proposing a molecular classification associated with hypercoagulation in ovarian clear cell carcinoma.

BACKGROUND: Although ovarian clear cell carcinoma (CCC) is associated with high incidence of thromboembolism, the clinicopathological and biological significance of hypercoagulable status in CCC remains unclear. MATERIALS AND METHODS: We retrospectively analyzed pretreatment D-dimer levels, thromboembolic status, and clinical outcome of 125 CCCs in the discovery set and 143 CCCs in two other independent validation sets. Next, we performed RNA sequencing of 93 CCCs and compared coagulation-related gene profiles with 2492 pan-cancer data. We investigated differences in molecular characteristics of CCC subclasses based on coagulation status. RESULTS: In the discovery dataset, D-dimer elevation above the normal range was significantly associated with shorter progression-free and overall survival, irrespective to thromboembolic status. Multivariate analysis identified D-dimer elevation and clinical stage as an independent prognostic factors. We confirmed the prognostic significance of D-dimer elevation in the validation sets. Tissue factor and IL6, which are considered key elements of cancer-induced hypercoagulation, were highly expressed in CCC than in other cancers regardless of D-dimer level. Higher activity of various oncogenic pathways was observed in CCC with compared to without D-dimer elevation. Moreover, hierarchical cluster analysis divided 57 CCCs with D-dimer elevation into immunologically hot and cold tumor subtypes. Hot tumors were characterized by enrichment of T-cell inflamed phenotype, inflammation, the epithelial-mesenchymal transition, and high serum levels of CRP, and cold tumors by enrichment of cell cycle and MYC pathways. CONCLUSIONS: CCC represents hypercoagulable disease and elevate D-dimer is a prognostic factor for decreased survival in CCC. D-dimer high CCC has distinct molecular characteristics into the inflammatory-driven pathway (hot tumor) and the immune-suppressive pathway (cold tumor). Treatment implication of our proposed molecular classification merits further investigation.

Academic Research Consortium for High Bleeding Risk Definitions for Early, Late, and Very Late Bleeding Events.

BACKGROUND: The validity of the Academic Research Consortium for High Bleeding Risk (ARC-HBR) definitions of early (<1 year), late (1-4 years), and very late (>4 years) bleeding events is unknown.Methods and Results:This study was performed on patients (n=3,453) implanted with second-generation drug-eluting stents (DES) between 2010 and 2013. Data on all criteria of the ARC-HBR definition were collected retrospectively. The primary endpoint was Bleeding Academic Research Consortium Type 3 or 5 bleeding events; the ischemic endpoint was a composite of cardiac death, myocardial infarction, and ischemic stroke. The mean follow-up period was 7.5 years. Compared with non-high bleeding risk (HBR) patients, HBR patients (n=1,840; 53.3%) had an increased risk of the primary endpoint (early events, 3.6% vs. 0.5% [P<0.0001]; late events, 5.3% vs. 2.5% [P<0.0001]; very late events, 5.5% vs. 2.1% [P<0.0001]) and of ischemic events during follow-up. The discrimination ability of the ARC-HBR definition for late and very late bleeding events was comparable to that of early bleeding events (C statistics 0.679, 0.621, and 0.620, respectively) with high negative predictive value (96.6%, 95.1%, and 93.1%, respectively). Multivariate analysis revealed the different effects of individual criteria on bleeding events in each follow-up period. CONCLUSIONS: The ARC-HBR definition consistently identified patients at risk of long-term bleeding and ischemic events after second-generation DES implantation.